Process for preparation of spirofluorenols

ABSTRACT

A spirofluorenol such as 3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene] is produced by protecting a hydroxyl group bonded to a particular fluorenone compound such as 3,9-dimethoxy-5-hydroxybenzo[c]fluorene-7-one with “a substituted silyl group in which the sum of carbon atoms of substituents bonded to a silicon atom is 5 to 12”, such as a t-butyldimethylsilyl group, then, reacting the fluorenone compound with a particular organometal compound such as 1-lithiophenanthrene so as to be transformed into a spiro form and, then, removing the protection therefrom. This method makes it possible to efficiently produce the spirofluorenol which is useful as a starting material for producing photochromic compounds.

BACKGROUND OF THE INVENTION

1. (Field of the Invention)

The present invention relates to a method of producing a spirofluorenolcompound useful as a starting material for producing a photochromiccompound.

2. (Description of the Related Art)

Recently, the chromene derivatives, especially spiroindenonaphthopyranesdraw much attention as photochromic compounds for their fast colordeveloping-fading rates, easy color tone controllability and high colorfastness. In these spiroindenonaphthopyranes, spiroketal type compounds(International Patent Publication No. 10-508031), biphenyl typespiro-compounds and phenanthrene type spiro-compounds (JapaneseUnexamined Patent Publication (Kokai) No. 2000-34418 and No.2001-192378) are known. In particular, the latter two compounds featurehigh color-developing sensitivity, fast fading rate and excellent colorfastness.

It has been known that these compounds are obtained by modifying theproperly substituted indenonaphthopyrane-one, prepared by several steps,represented by the following formula (5) (Japanese Unexamined PatentPublication (Kokai) No. 2000-34418 and No. 2001-192378). However,according to the above method, a strict purification must be needed toobtain desired developing color tone because a trace of impurity mayexhibits photochromic properties and may developing undesired color tonewhen using the indenonaphthopyrane-one, it exhibits photochromicproperties by itself, as the intermediate.

On the other hand, it has been known another method, which is littlelikely to form photochromic impurities, for producing desired chromenederivatives from spirofluorenol (Japanese Unexamined Patent Publication(Kokai) No. 2001-192378).

According to the above method, a hydroxyfluorenone having a phenolichydroxyl group is reacted with a Grignard reagent, and then reactedunder acidic condition to form spirofluorenol. As a result, excessamounts of Grignard reagent is required to complete the former reaction.

SUMMARY OF THE INVENTION

Therefore, the present invention provides an efficient method ofproducing a spirofluorenol which is useful as a starting material forproducing the photochromic compounds.

By protecting a hydroxyl group of the hydroxyfluorenone, the presentinventors have attempted to decrease the amount of organometal reagentssuch as Grignard reagent used during the course of producing thespirofluorenols, and have studied the effect of various protectinggroups, As a result, the inventors have discovered that only aparticular protecting group can be introduced with a high selectivityand a high conversion, and that the particular protecting group isdurable under the condition of the next step, and that the particularprotecting group can be easily removed in good yield, and have finishedthe invention.

According to the present invention, this is provided a method ofproducing a spirofluorenol compound represented by the following formula(1),

by protecting a hydroxyl group bonded to a fluorenone compoundrepresented by the following formula (2),

with a protecting group which is a substituted silyl group in which thesum of carbon atoms of substituents bonded to a silicon atom is 5 to 12,then, reacting the fluorenone compound with an organometal compoundrepresented by the following formula (3),

wherein M is Li, MgCl, MgBr, MgI or CuLi, to thereby obtain ahydroxy-arylfluorenol of which the hydroxyl group is protected with saidprotecting group, and transforming the obtained hydroxy-arylfluorenolinto a spiro form and removing the protection therefrom, wherein in theabove formulas (1) to (3):

X is either a single bond or a divalent group selected from thefollowing group A;

Y is a group forming an aromatic hydrocarbon cyclic group or anunsaturated heterocyclic group together with two carbon atoms of a benzoring;

when X is a single bond, R¹ and R² are, respectively, hydrogen atoms ormonovalent groups selected from the following group B, or are bondedtogether to form a divalent group selected from the following group A(except, -Z- and —CR⁵R⁶—);

when X is a group selected from the group A, R¹ and R² are,respectively, hydrogen atoms or monovalent groups selected from thefollowing group B;

R³ and R⁴ are, respectively, hydrogen atoms or monovalent groupsselected from the following group B; and

p and q are, independently from each other, integers of 0 to 3;

group A:

-   -   -Z-, —(CR⁵R⁶)_(n)—, —(CR⁵R⁶)_(m)-Z-, -Z-(CR⁵R⁶)_(l)-Z-,        —(CR⁵R⁶)_(a)-Z-(CR⁵R⁶)_(b)—, —(CR⁵═CR⁶)_(k)—, and CR⁵═N— wherein        -Z- is —O—, —S— or —NR⁵—, R⁵ and R⁶ are, independently from each        other, hydrogen atoms, or monovalent groups selected from the        following group B, wherein when there are a plurality of -Z-, R⁵        or R⁶ in one group, the plurality of -Z-, R⁵ or R⁶ may be        different from each other, and a, b, k and l are, independently        from each other, integers of 1 to 4, and m and n are,        independently from each other, integers of 1 to 6;        group B:    -   alkyl group, aralkyl group, substituted or unsubstituted aryl        group, hydroxy group, alkoxy group, aralkoxy group, amino group,        monosubstituted amino group, disubstituted amino group, cyano        group, nitro group, halogen atom, trufluoromethyl group,        substituted or unsubstituted heterocyclic group having a bond on        a carbon atom or on a nitrogen atom, and substituted or        unsubstituted condensed heterocyclic group, aromatic hydrocarbon        ring or hetero ring in condensed thereto and having a bond on a        carbon atom or on a nitrogen atom.

DETAILED DESCRIPTION OF THE INVENTION

(Object Product to be Produced)

A spirofluorenol compound represented by the above formula (1) producedby a production method of the present invention is useful as a startingmaterial for the synthesis of a photochromic compound that comprises achromene derivative.

In the above formula (1), X is either a single bond or a divalent groupselected from the above group A.

Further, groups in the above group B serve not only as R⁵ or R⁶ in thegroup A but also as R¹, R², R³ or R⁴ in the above formula (1). Preferredexamples of the group in the group B include alkyl groups having 1 to 6carbon atoms, such as methyl group, ethyl group, isopropyl group,t-butyl group and cyclohexyl group; aralkyl groups having 7 to 20 carbonatoms, such as benzyl group, phenethyl group and trityl group;substituted or unsubstituted aryl groups, such as phenyl group, naphthylgroup and alkoxyphenyl group; hydroxyl group; alkoxy groups having 1 to6 carbon atoms, such as methoxy group and t-butoxy group; aralkoxygroups having 7 to 20 carbon atoms, such as benzyloxy group andtrityloxy group; amino group; monosubstituted amino groups having 1 to 6carbon atoms, such as methylamino group and cyclohexylamino group;disubstituted amino groups having 1 up to 20 carbon atoms, such asdimethylamino group and dicyclohexylamino group; cyano group; nitrogroup; halogen atoms, such as chlorine atom and bromine atom;trifluoromethyl group; substituted or unsubstituted heterocyclic groups,such as 2-oxazolyl group, 4-morpholino group, and2,2,6,6-tetramethyl-1-piperidino group; and substituted or unsubstitutedcondensed heterocyclic groups, such as 2-benzoxazolyl group,1-benzotriazolyl group, 9-carbazolyl group and 8-quinolyl group.

When X is a single bond in the above formula (1), R¹ and R² are,respectively, hydrogen atoms, groups selected from the group B, orgroups that are bonded together to form a group represented by the groupA. That is, when X is a single bond, the compound of the above formula(1) possesses a 9,9′-spirobifluorene skeleton. For example, when R¹ andR² are bonded together, then, —CR⁵═CR⁶— that is formed, the compoundpossesses a spiro[fluorene-9,1′-(1H-cyclopent[d,e,f]phenanthrene)]skeleton. However, it never takes place from the steric requirement thatR¹ and R² are bonded together to form -Z- (i.e., —O—, —S— or —NR⁵—) or—CR⁵R⁶—.

Further, when X is a divalent group selected from the group A, R¹ and R²are, respectively, hydrogen atoms or groups selected from the group B.In this case, the compound represented by the above formula (1)possesses a spiro[fluorene-9,9′-xanthene] skeleton (when X is —O—), aspiro[fluorene-9,9′-(9,10-dihydroacridine] skeleton (when X is —NH—), ora spiro[fluorene-9,9′-(9,10-dihydroanthracene] skeleton (when X is—CH₂—). However, there is no particular steric limitation on R¹ and R².

In the above formula (1), Y is a group that forms an aromatichydrocarbon group or an unsaturated heterocyclic group together with twocarbon atoms of a benzo ring. When Y forms an aromatic hydrocarbongroup, the compound of the formula (1) possesses, for example, abenzofluorenol skeleton or a naphthofluorenol skeleton. When Y forms anunsaturated heterocyclic group, the compound of the formula (1)possesses, for example, a furofluorenol skeleton or an indolofluorenolskeleton. Here, the place and direction of ring condensation are quitearbitrary.

In the above formula (1), further, R³ and R⁴ are monovalent groups inthe above group B, and p and q representing the numbers of R³ and R⁴ areintegers of 0 to 3, respectively. When p or q is 2 or 3, i.e., when R³or R⁴ is existing in a plural number, the plurality of R³ or R⁴ may bedifferent from each other.

(Production of the Spirofluorenol Compounds)

Starting Materials:

To produce the spirofluorenol compound of the above-mentioned formula(1) according to the present invention, first, a hydroxyl group bondedto a fluorenone compound represented by the formula (2),

-   -   wherein Y, R³, R⁴, p and q are as defined in the formula (1),        is protected with a protecting group which is a substituted        silyl group. Here, when the compound of the formula (2) contains        an amino group or a monosubstituted amino group, the amino group        or the monosubstituted amino group, too, is protected with the        substituted silyl group in addition to the hydroxyl group. The        hydroxyl group to be protected is not limited to the one bonded        to the 2-position of the fluorenone ring but includes a hydroxyl        group bonded to any other position. When R³ or R⁴ is a hydroxyl        group, an amino group or a monosubstituted amino group, then,        the above group is protected with the substituted silyl group in        addition to the hydroxyl group bonded to the 2-position of the        fluorenone ring. Hereinafter, the group that is to be protected        is often called to-be-protected functional group.

There is no particular limitation on the hydroxyfluorenone used as thestarting material provided it is the one represented by the aboveformula (2). Desirably, however, the hydroxyfluorenone used as thestarting material is the one in which Y is a condensed benzo ring (i.e.,the one having a hydroxybenzofluorenone skeleton) from the standpoint ofperformance of the object photochromic compound. From the standpoint ofperformance of the object photochromic compound, further, it is desiredthat R³ and R⁴ are alkyl groups having 1 to 6 carbon atoms, such asmethyl groups, ethyl groups, isopropyl groups, t-butyl groups andcyclohexyl groups; aralkyl groups having 7 to 20 carbon atoms, such asbenzyl groups, phenethyl groups and trityl groups; substituted orunsubstituted aryl groups, such as phenyl groups, naphthyl groups andalkoxyphenyl groups; hydroxy groups; alkoxy groups having 1 to 6 carbonatoms, such as methoxy groups and t-butoxy groups; or aralkoxy groupshaving 7 to 20 carbon atoms, such as benzyloxy groups and trityloxygroups; and p and q are 0 or 1.

Concrete examples of the hydroxyfluorenone of the formula (2) that canbe favorably used in the present invention include3-methoxy-5-hydroxybenzo[c]fluorene-7-one,9-methoxy-5-hydroxybenzo[c]fluorene-7-one and3,9-dimethoxy-5-hydroxybenzo[c]fluorene-7-one.

Introduction of Protecting Groups:

In the present invention, a substituted silyl group is used as aprotecting group for protecting the above-mentioned to-be-protectedfunctional group. Here, the greatest feature resides in that the sum ofcarbon atoms of three substituents bonded to a silicon atom is 5 to 12.That is, by using the substituted silyl group having a large sterichindrance as a protecting agent, the selectivity and the conversion areboth maintained high at the time of introducing the protecting group,the protecting group is not removed in the next step of reaction, theyield is improved at the time of removing the protection and, as aresult, a spirofluorenol which is a desired compound is efficientlyproduced.

Various protecting groups have been proposed for protecting the hydroxylgroup, such as methyl group, benzyl group, as well as methoxymethylgroup and tetrahydropyranyl group which are of the acetal type; acetylgroup and benzoyl group which are of the ester type; benzyloxycarbonylgroup and t-butoxycarbonyl group which are of the carbonate type; andtrimethylsilyl group which is of the silyl ether type. When the methylgroup is used as the protecting group, however, the alkoxy group isdestroyed in the step of removing the protecting group if R³ or R⁴ ofhydroxyfluorenone is an alkoxy group such as methoxy group, which,therefore, cannot serve as a general method of production. When thebenzyl group is used as the protecting group, the benzyl is introducednot only to the hydroxyl group to which the protecting group is to beintroduced but also to the molecular skeleton. In the step of removingthe protecting group (for removing protection), therefore, sidereactions take place much, such as destroying the alkoxy group andreducing the molecular skeleton, which is not efficient. The protectiongroup of the acetal type involves problems, too, in regard toselectivity at the time of introducing the protecting group. Theprotecting groups of the ester type and of the carbonate type cannotwithstand the reaction condition in the next step. Even the protectinggroup of the silyl ether type cannot withstand the reaction of the nextstep if it has a sterically simple structure like the trimethylsilylgroup and cannot, hence, be used.

There is no particular limitation on the substituted sily group used asa protecting group in the invention provided it satisfies a conditionthat the sum of carbon atoms of three substituents is 5 to 12. It is,however, particularly desired to use t-butyldimethylsilyl group,triisopropylsilyl group or 2-methyl-3,3-dimethyl-2-butyldimethylsilylgroup from such a standpoint that a silylating agent used forintroducing the protecting group is easily available and is effective aswill be described later.

The silylating agent used for introducing the protecting group is acompound in which the substituted silyl group is bonded to aneliminating group, and is a compound represented by, for example, thefollowing formula (6),E-SiR⁷R⁸R⁹  (6)

-   -   wherein E is an eliminating group, and R⁷, R⁸ and R⁹ are alkyl        groups, the sum of carbon atoms of the alkyl groups being 5 to        12.

As the eliminating group, there can be exemplified a halogen atom, anazide group, an alkoxy group, an arylsulfonyloxy group and atrialkylsilylamino group having the total number of carbon atoms of notsmaller than 5. Among the silylating agents represented by the aboveformula (6), it is desired to use chlorinated silicon compound such ast-butyldimethylsilyl chloride, triisopropylsilyl chloride, or2-methyl-3,3-dimethyl-2-butyldimethylsilyl chloride from the standpointof availability.

That is, upon reacting the above silylating agent with thehydroxyfluorenone of the formula (2), a protecting group which is thesubstituted silyl group is introduced to protect the to-be-protectedfunctional group as represented by the hydroxyl group.

Though there is no particular limitation on the reaction conditions atthe time of protection, a solvent is usually used, and a tertiary aminecompound is added to a mixed solution of the hydroxyfluorenone and thesilylating agent to conduct the reaction while trapping the acid formedduring the reaction thereby to introduce the protecting group. Or, ahydroxyl group of the hydroxyfluorenone is reacted with sodium hydride,potassium t-butoxide, sodium hydroxide or potassium hydroxide to form analkali metal salt thereof which is, then, reacted with the silylatingagent to introduce the protecting group. It is allowable to use theabove two methods in combination to carry out the reaction, as a matterof course.

There is no particular limitation on the solvent used here provided itdoes not react with the silylating agent. Examples include aromatichydrocarbons such as toluene and xylene; chlorinated hydrocarbons suchas dichloromethane and chloroform; acyclic or cyclic ethers such asdiethyl ether and tetrahydrofurane; nitriles such as acetonitrile andbutyronitrile; acyclic or cyclic amide such as dimethylformamide andN-methylpyrrolidone; acyclic or cyclic sulfoxide such as dimethylsulfoxide and sulforane; or a mixed solvent thereof.

As the tertiary amine compound, though there is no particularlimitation, there can be used acyclic or cyclic aliphatic tertiaryamines such as triethylamine and n-methylmorpholine; aromatic tertiaryamines such as dimethyl aniline and methyl diphenylamine; andheterocyclic tertiary amines such as pyridine and4-dimethylaminopyridine. Among them, it is desired to use a tertiaryamine compound having a structure represented by the following formula(4),

-   -   wherein i is an integer of 2 to 4, and j is an integer of 3 to        6,        such as 1,8-diazabicyclo[5,4,0]undeca-7-ene or        1,7-diazabicyclo[4,3,0]nona-6-ene from the standpoint of high        selectivity and high conversion. It is further allowable to use        the tertiary amine compound represented by the above formula (4)        in a catalytic amount in combination with other tertiary amine        compounds.

There is thus obtained a hydroxyfluorenone of which the to-be-protectedfunctional group such as a hydroxyl group is protected. This compoundcan be isolated and refined according to conventional methods but canalso be directly used for the next reaction.

Reaction with an Organometal Compound:

According to the production method of the present invention, thehydroxyfluorenone protected with the substituted silyl group obtainedabove is reacted with an organometal compound represented by the formula(3),

-   -   wherein M is Li, MgCl, MgBr, MgI or CuLi, and X,    -   R¹ and R² are as defined in the formula (1),        to prepare a hydroxyl-protected-arylfluorenol. In carrying out        the reaction, the to-be-protected functional group such as the        hydroxyl group bonded to the 2-position of the fluorenone ring        has been protected by the substituted silyl group, and does not        take part in the reaction with the organometal compound, and        only the carbonyl group (C═O) reacts with the organometal        compound. Therefore, the obtained        hydroxy-protected-arylfluorenol is expressed by, for example,        the following formula (7), and the hydroxyl group and the like        groups have been protected by the substituted silyl groups.

In the above formula (7), when R³ or R⁴ is a hydroxyl group, amino groupor a monosubstituted amino group, then, this group, too, is protected bythe protecting group (substituted silyl group, —SiR⁷R⁸R⁹).

The organometal compound used for the above reaction is obtained byreacting a halogen compound having a molecular structure correspondingto the molecular skeleton of the formula (3) with an organolithiumcompound such as butyl lithium, or with lithium metal, magnesium metalor alkyl copper lithium compound. The organometal compound can befurther produced even by reacting an organolithium compound having amolecular structure corresponding to the molecular skeleton of theformula (3) with a copper compound.

The reaction of the hydroxyfluorenone of which the hydroxyl group isprotected with the organosilyl compound is carried out by reacting theorganometal compound produced as described above with thehydroxyfluorenone of which the hydroxyl group and the like groups havebeen protected without isolating the organometal compound. There is noparticular limitation on the solvent used for the reaction provided itdoes not react with the organometal compound, and there can be usedacyclic or cyclic aliphatic hydrocarbon such as hexane or cyclohexane;aromatic hydrocarbon such as toluene or xylene; or acyclic or cyclicether such as diethylether or tetrahydrofurane; or a mixed solventthereof. Though there is no particular limitation, the reactiontemperature may be from −10° C. to about a boiling point of the solvent,and the reaction time may be from 0.5 hours to about 10 hours, which maybe determined while making sure the progress of the reaction. After thereaction, the reaction product is quenched with water to obtain ahydroxy-arylfluorenol of which the hydroxyl group and the like groupsare protected. The thus obtained hydroxy-arylfluorenol of which thehydroxyl group and the like groups are protected can be isolated andrefined by conventional methods, but can also be directly used for thenext reaction.

Transforming Into a Spiro Form and Removing the Protection:

In the present invention, the “hydroxy-arylfluorenol of which thehydroxyl group and the like groups are protected” obtained as describedabove is transformed into a spiro form under an acidic condition toobtain a spirofluorenol of which the to-be-protected functional groupsuch as hydroxyl group and the like groups are protected with thesubstituted silyl groups.

An acid is used for establishing an acidic condition. As the acid, therecan be used known acids without limitation, e.g., inorganic acids suchas sulfuric acid and phosphoric acid; organic acids such asp-toluenesulfonic acid and trifluoroacetic acid; inorganic Lewis acidssuch as aluminum chloride, titanium tetrachloride, silicontetrachloride, tin chloride and iron chloride; and solid acids such asacidic alumina and acidic ion-exchange resin. There can be further useda dehydrating agent that forms an acid upon reacting with water, such asphosphorus pentoxide, phosphorus pentachloride, thionyl chloride andsulfuryl chloride. The amount of the acid that is used differs dependingupon its kind and there is no particular limitation. In general,however, the acid is used in an amount of 0.01 to 1000 parts by weightand, more preferably, 1 to 50 parts by weight per 100 parts by weight ofthe hydroxy-arylfluorenol.

The spiro-reaction is conducted under the acidic condition usually in asolvent. There is no particular limitation on the solvent used hereprovided it does not react with the acid that is used, and there can bedesirably used an acyclic or cyclic aliphatic hydrocarbon such as hexaneor cyclohexane, aromatic hydrocarbon such as toluene or xylene,chlorinated hydrocarbon such as dichloromethane or chloroform, cyclicether such as tetrahydrofurane, esters such as ethyl acetate or butylacetate, or nitrites such as acetonitrile. Though there is no particularlimitation, the reaction temperature may be from room temperature toabout a boiling point of the solvent, and the reaction time may be from0.5 hours to about 10 hours, which may be determined while making surethe progress of the reaction. Here, the protection group (substitutedsilyl group) may be removed depending upon the conditions, which,however, does not affect the subsequent steps. The thus obtainedspirofluorenol of which the hydroxyl group is protected can be isolatedand refined by conventional methods, but can also be directly used forthe next reaction.

In the production method of the present invention, finally, thespirofluorenol of which the hydroxyl group and the like groups areprotected obtained as described above is subjected to the removal ofprotection (removal of the substituted silyl group). Though there is noparticular limitation, the method of removing the protection is easilyconducted by the reaction with a protection-removing agent containingfluorine anions in a solvent.

As the protection-removing agent containing fluorine anions, there canbe used quaternary ammonium fluorides such as tetrabutylammoniumfluoride, benzyltrimethylammonium fluoride; and alkali metal fluoridessuch as sodium fluoride and potassium fluoride. When an alkali metalfluoride is used as the protection-removing agent, it is desired to alsouse a quaternary ammonium salt such as tetrabutylammonium bromide orbenzyltrimethylammonium chloride in combination. There is no particularlimitation on the solvent that is used provided it does not impair thereaction. Examples include acyclic or cyclic aliphatic hydrocarbons suchas hexane and cyclohexane; aromatic hydrocarbons such as toluene andxylene; chlorinated hydrocarbons such as dichloromethane and chloroform;acyclic or cyclic ethers such as diethyl ether and tetrahydrofuran;nitrites such as acetonitrile and butyronitrile; alcohols such asmethanol and ethanol; acyclic or cyclic amides such as dimethylformamideand N-methylpyrrolidone; acyclic or cyclic sulfoxide; sulfone such asdimethylsulfoxide and sulforane; or a mixed solvent thereof. Thesesolvents may contain water.

In order to remove the protection, further, there can be easily employeda method of reacting the spirofluorenol of which the hydroxyl group andthe like groups are protected with a compound of the above formula (4)together with alcohols or water. The solvent used here may be theabove-mentioned solvent. Desirably, however, alcohols are used as asolvent so as to also serves as a reaction reagent.

It is also possible to remove the protection by using a Lewis acid suchas boron trifluoride. There is no particular limitation on the solventprovided it is not decomposed by acid. Chlorinated hydrocarbons can bepreferably used.

The spirofluorenol obtained by removing the protection can be isolatedand refined according to conventional methods, but can also be directlyused for the reaction for synthesizing a photochromic compound.

According to the production method of the present invention, further, itis possible to conduct the spiro-reaction and the protection-removingreaction in a single step by using an acid. Employment of this method isparticularly preferred from the standpoint of improving the efficiency.In this case, preferred examples of the acid include organosulfonicacid, organic acid or Lewis acid and, particularly, p-toluenesulfonicacid, trifluoroacetic acid, boron trifluoride (usually used as an ethercomplex), magnesium bromide or aluminum chloride among the acidsexemplified above for being used for the spiro-reaction and theprotection-removing reaction. There can be used any solvent withoutlimitation provided it can be used for the spiro-reaction or theprotection-removing reaction. From the standpoint of selectivity of thereaction, however, acetonitrile is most desired. After the reaction, theacid is inactivated and is washed by adding water or a saline solutionthereto and, then, the solvent is removed from the organic layer tothereby obtain an object product.

The production method of the present invention makes it possible toefficiently produce the spirofluorenol compound useful as a startingmaterial for producing a photochromic compound.

EXAMPLES

The present invention will now be described in detail by way of WorkingExamples to which only, however, the invention is in no way limited.

Example 1

2 Grams (6.5 mmols) of a 3,9-dimethoxy-5-hydroxybenzo[c]fluorene-7-onewas suspended in 10 ml of a tetrahydrofuran (THF) followed by theaddition of a methanol solution (40 ml) containing 0.31 g (7.8 mmols) ofsodium hydroxide, and the mixture was stirred at room temperature forone hour. After 80 ml of toluene was added, the solvent was alldistilled off under a reduced pressure to obtain a sodium salt. Thesodium salt was dissolved in 50 ml of the THF, and a THF (20 ml)solution containing 1.2 g (7.8 mmols) of a t-butyldimethylsilyl chloridewas added dropwise thereto to conduct the reaction at room temperaturefor 2 hours. The conversion was 99%.

Then, the THF was distilled off under a reduced pressure, and 2.4 g of a3,9-dimethoxy-5-t-butyldimethylsilyloxybenzo [c] fluorene-7-one (purity,97%; yield, 87%)(abbreviated as DBBF) was crystallized from 30 ml ofmethanol.

2.1 Grams (8.3 mmols) of a 1-bromophenanthrene was dissolved in 43 ml ofheptane, 5.3 ml (1.6 mols/l, 8.5 mmols) of butyl lithium was addedthereto at room temperature to obtain a 1-lithiophenanthrene, which wascooled down to −5° C., followed by the addition of 2.2 g (5.2 mmols) ofthe above DBBF. The mixture was stirred for one hour and to which wasfurther added the THF at a temperature of not higher than 0° C. Themixture was stirred at this temperature for 2 hours. The conversion was99%.

After the reaction, the reaction product was washed with 8.5 ml of 1Nhydrochloric acid and 10 ml of water, and the solvent was distilled offunder a reduced pressure. 2.5 Grams of a3,9-dimethoxy-5-t-butyldimethylsilyloxy-7-hydroxy-7-phenanthrene-1-ylbenzo[c]fluorene(purity, 97%; yield, 82%)(abbreviated as DBHPBF) was crystallized from20 ml of methanol.

Of the obtained 2.5 g of DBHPBF, 1.0 g (1.7 mmols) thereof was suspendedin 10 g of acetic acid and was heated at 60° C. Here, a solutioncomprising 3.5 g of acetic acid, 0.7 g of concentrated sulfuric acid and2.1 g of water was added thereto, and the mixture was stirred at 60° C.for 3 hours. The conversion was 99%.

The mixture was, then, cooled, adding 50 ml of THF and washed with 46 mlof a 5N sodium hydroxide aqueous solution, and was further washed twotimes each with 20 ml of water, and the solvent was distilled off undera reduced pressure. 0.87 Grams of a3′,9′-dimethoxy-5′-t-butyldimethylsilyloxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene] (purity, 96%;yield, 90%)(abbreviated as DBCPBF) was crystallized from 30 ml ofmethanol.

Of the obtained 0.87 g of DBCPBF, 0.58 g (1.0 mmol) thereof wasdissolved in 30 ml of the THF, followed by the addition of 1.3 g (4mmols) of a tetrabutylammonium bromide and 0.23 g (4 mmols) of potassiumfluoride, and the mixture was heated and refluxed for 10 hours. Theconversion was 98%. The mixture was cooled and was washed three timeseach with 10 ml of water, and the solvent was distilled off under areduced pressure. 0.47 Grams (yield, 100%) of a3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene]having a purity of 95% was obtained. The total yield was calculated tobe 64%.

Comparative Example 1

0.28 Grams (7 mmols) of sodium hydroxide was dissolved in 20 ml ofmethanol, and to which were added 2 g (6.6 mmols) of a3,9-dimethoxy-5-hydroxybenzo[c]fluorene-7-one, 0.82 g (6.5 mmols) of abenzyl chloride and 20 ml of the THF, and the mixture was refluxed for20 hours. The conversion was 90%. A by-product was formed during thereaction presumably due to the reaction of two benzyl groups. Thesolvent was distilled off under a reduced pressure, and 1.4 g of a3,9-dimethoxy-5-benzyloxybenzo[c]fluorene-7-one (purity, 97%; yield,52%) was crystallized from 32 ml of acetone.

The phenanthrene addition reaction and the dehydration reaction wereconducted in accordance with Example 1 to obtain a3′,9′-dimethoxy-5′-benzyloxyspiro[(1H-cyclopent[d,e,f]phenanthrene-1,7′-benzo[c]fluorene](abbreviatedas spirobenzofluorene). The purity and the yield were 85% and 90%,respectively.

0.67 Grams (1.2 mmols) of the obtained spirobenzofluorene was dissolvedin 30 ml of THF and 50 ml of methanol, and to which were added 0.27 g of5% palladium on charcoal and 15.1 g (240 mmols) of ammonium formate, toconduct the reaction at room temperature for 2 hours. The conversion was99%. After the reaction, palladium on charcoal was separated byfiltration, washed with 20 ml of water, and the solvent was distilledoff under a reduced pressure. 0.55 Grams (yield, 99%) of a3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f])phenanthrene]-1,7′-benzo[c]fluorene]having a purity of 98% was obtained. The total yield was calculated tobe 39%.

Comparative Example 2

10 Grams (32.6 mmols) of a 3,9-dimethoxy-5-hydroxybenzo[c]fluorene-7-onewas suspended in 500 ml of the THF followed by the addition of 10.7 g(49 mmols) of a di-t-butyl dicarbonate and 0.04 g (0.3 mmols) of a4-dimethylaminopyridine, and the mixture was stirred at room temperaturefor 3 hours. The THF was concentrated until crystals precipitated, andto which was added 400 ml of heptane to crystallize 12.8 g of a3,9-dimethoxy-5-t-butoxycarbonyloxybenzo[c]fluorene-7-one (abbreviatedas benzofluorenone)(purity, 96%; yield 97%).

The above benzofluorenone was reacted with the 1-lithiophenanthrene inthe same manner as in Example 1, whereby the t-butoxycarbonyl group hasreacted and the purity has dropped down to 61%. The dehydration reactionwas conducted in the same manner as in Example 1, and it was found thatthe protection-removing reaction has occurred simultaneously. However, A3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene]having a purity of only 44% was obtained. This compound could not berefined. Or, if it were refined without loss, the whole yield wascalculated to be 43%.

Example 2

10 Grams (36.2 mmols) of a 3-methoxy-5-hydroxybenzo[c]fluorene-7-one wassuspended in 150 ml of the THF followed by the addition of 4.4 g (43.5mmols) of a triethylamine. Then, a solution obtained by dissolving 6.55g (43.5 mmols) of a t-butyldimethylsilyl chloride in 50 ml of the THFwas added thereto dropwise at room temperature, and the mixture wasstirred at 45° C. for 6 hours. The conversion was 98%. The THF wasdistilled off under a reduced pressure and crystallize 12 g of a3-methoxy-5-t-butyldimethylsilyloxybenzo[c]fluorene-7-one (abbreviatedas MBBF)(purity, 98%; yield, 85%) from 230 ml of methanol.

10.9 Grams (38.9 mmols) of a 2-biphenyl iodide was dissolved in 150 mlof heptane and was cooled down to −5° C. 26.5 ml (1.6 mols/l, 42.4mmols) of butyl lithium was added thereto, and the mixture was stirredat −5° C. for one hour. 10.5 Grams (27 mmols) of MBBF prepared above wasadded thereto, and the THF was added thereto at a temperature of nothigher than 0° C., and the mixture was stirred at this temperature for 2hours. The conversion was 99%. After the reaction, 200 ml of the THF wasadded to the reaction product and obtained solution was washed with 42ml of 1N hydrochloric acid, and was further washed twice each with 50 mlof water. The solvent was distilled off under a reduced pressure toobtain 14 g of a3-methoxy-5-t-butyldimethylsilyloxy-7-hydroxy-7-(2-phenylphenyl)benzo[c]fluorene(abbreviated as MBHPBF)(purity, 95%; yield, 95%).

Of the obtained 14 g of MBHPBF, 10.9 g (20 mmols) thereof was suspendedin 115 g of acetic acid and was heated at 60° C. Here, a solutioncomprising 55 g of acetic acid, 10.9 g of concentrated sulfuric acid and32.6 g of water was added thereto, and the mixture was stirred at 60° C.for 3 hours. The conversion was 99%. The mixture was, then, cooled downto 30° C. and 400 ml of ethyl acetate was added thereto, and obtainedsolution was washed with 740 ml of a 5N sodium hydroxide aqueoussolution, and was further washed 200 ml of a 10% saline solution. Thesolvent was distilled off to obtain 10 g of a3′-methoxy-5′-t-butyldimethylsilyloxyspiro[fluorene-9,7′-benzo[c]fluorene](abbreviatedas MBSFBF)(purity, 95%; yield, 95%).

Of the obtained 10 g of MBSFBF, 0.53 g (1 mmol) thereof was dissolved in30 ml of the THF, followed by the addition of 1.52 g (10 mmols) of a1,8-diazabicyclo[5,4,0]undeca-7-one, and the mixture was stirred at roomtemperature for 24 hours. The conversion was 99%. The reaction productwas, then, washed with 10 ml of 1N hydrochloric acid and was furtherwashed three times each with 10 ml of water. The THF was distilled offto obtain 0.41 g of a 3′-methoxy-5′-hydroxyspiro[fluorene-9,7′-benzo[c]fluorene](purity, 96%; yield, 99%). The total yield was calculated tobe 76%.

Example 3

A 3′-methoxy-5′-t-butyldimethylsilyloxyspiro[fluorene-9,7′-benzo[c]fluorene](abbreviated as MBSFBF) was obtained incompliance with Example 2.

0.53 Grams (1 mmol) of the above MBSFBF was dissolved in 30 ml ofchloroform, cooled down to 5° C., and to which was added 3.4 g (24mmols) of a diethyl ether complex of boron trifluoride to conduct thereaction at 50° C. for 20 hours. The conversion was 99%. Thereafter, thereaction product was cooled and washed with 24 ml of 1N sodium hydroxideaqueous solution and four times each with 50 ml of water.

The chloroform was distilled off to obtain 0.40 g of a3′-methoxy-5′-hydroxyspiro[fluorene-9,7′-benzo[c]fluorene](purity, 96%;yield 97%). The total yield was calculated to be 74%.

Comparative Example 3

0.4 Grams (10 mmols) of sodium hydroxide was dissolved in 10 ml ofmethanol, and to which were added 2.5 g (9.1 mmols) a3-methoxy-5-hydroxybenzo[c]fluorene-7-one, 30 ml of the THF and 3.7 g(29 mmols) of a benzyl chloride, and the mixture was stirred at 60° C.for 10 hours. The conversion was 95%.

Thereafter, the mixture was cooled down to 20° C., and the precipitatedcrystals were filtered, washed with 10 ml of water, and were dried toobtain 2.0 g of a 3-methoxy-5-benzyloxybenzo[c]fluorene-7-one (purity,99%; yield, 61%).

The biphenyl addition reaction and the dehydration reaction wereconducted in accordance with Example 2 to obtain 2.5 g of a3′-methoxy-5′-benzyloxyspiro[fluorene-9,7′-benzo[c]fluorene](abbreviatedas MBOSFBF). The purity and the yield were 97% and 95%, respectively.

0.5 Grams (1 mmol) of the above MBOSFBF was dissolved in a mixed solventof 50 ml of THF, 10 ml of acetic acid, 5 ml of methanol and 1.5 ml ofwater, and to which was added 0.05 g of 5% palladium on charcoal. Themixture was stirred under hydrogen atmosphere by using a hydrogenballoon at 40° C. for 24 hours. The conversion was 99%. After thereaction, the reaction product was cooled, palladium on charcoal wasseparated by filtration, and the solvent was removed by distillationunder a reduced pressure to obtain 0.41 g of a3′-methoxy-5′-hydroxyspiro[fluorene-9,7′-benzo[c]fluorene](purity, 98%;yield, 98%). The total yield was calculated to be 55%.

Example 4

A3,9-dimethoxy-5-t-butyldimethylsilyloxy-7-hydroxy-7-phenanthrene-1-ylbenzo[c]fluorene](abbreviatedas DBHPBF) was obtained in compliance with Example 1.

1.0 Gram (1.7 mmols) of the above DBHPBF was dissolved in 70 ml ofacetonitrile, and to which was added 0.71 g (5 mmols) of an ethercomplex of boron trifluoride, and the mixture was stirred at 50° C. for3 hours. 0.32 Grams (5.5 mmols) of potassium fluoride was added toinactivate the ether complex of boron trifluoride and, after 90 ml ofTHF was added, the reaction product was washed three times each with 80ml of a 10% of saline solution. The solvent was distilled off under areduced pressure to obtain 0.46 g (yield, 98%) of a3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene]having a purity of 98%. The total yield was calculated to be 63%.

Examples 5 to 11

The3,9-dimethoxy-5-t-butyldimethylsilyloxy-7-hydroxy-7-phenanthrene-1-ylbenzo[c]fluorenewas subjected to the spiro-reaction and to the protection-removingreaction in compliance with Example 4 under the conditions shown inTable 1 to obtain the results shown in Table 1.

Comparative Example 4

2.1 Grams (8.3 mmols) of a 1-bromophenanthrene was dissolved in 43 ml ofheptane, and to which was added 5.3 ml (1.6 mols/l, 8.5 mmols) ofbutyllithium to obtain a 1-lithiophenanthrene, which was, then, cooleddown to −5° C. 1.6 Grams (5.2 mmols) of the3.9-dimethoxy-5-hydroxybenzo[c]fluorene-7-one was added thereto, and themixture was stirred for one hour. Then, THF was added thereto at atemperature of not higher than 0° C., and the mixture was stirred atthis temperature for 2 hours. The conversion was 40%. The mixture wascontinuously stirred for another 20 hours, but the conversion remainedto be 40%.

After the reaction, the reaction product was washed with 8.5 ml of 1Nhydrochloric acid and 10 ml of water, and the solvent was distilled offunder a reduced pressure. 0.81 Grams of a3,9-dimethoxy-5-hydroxy-7-hydroxy-7-phenanthrene-1-ilbenzo[c]fluorene(abbreviatedas DHHPBF)(purity, 92%; yield, 32%) was crystallized from 20 ml ofmethanol.

Of the obtained DHHPBF, 0.5 g (1.0 mmol) thereof was suspended in 5.9 gof acetic acid, and was heated at 60° C. A solution comprising 2.1 g ofacetic acid, 0.4 g of concentrated sulfuric acid and 1.2 g of water wasadded thereto, and the mixture was stirred at 60° C. for 3 hours. Theconversion was 99%.

Then, the mixture was cooled and was washed with 27 ml of 5N sodiumhydroxide and 30 ml of THF, and was further washed twice each with 13 mlof water, and the solvent was distilled off under a reduced pressure.0.2 Grams of a3′,9′-dimethoxy-5′-hydroxyspiro[(1H-cyclopent[d,e,f]phenanthrene)-1,7′-benzo[c]fluorene]was crystallized from 17 ml of methanol (purity 95%; yield, 40%). Thetotal yield was calculated to be 13%.

TABLE 1 Starting Amount Example material Solvent of acid TemperatureTime Purity Yield No. (mmol) (60 ml) Acid (mmol) (° C.) (hr) (%) (%) 51.67 acetonitrile boron trifluride 16.7 25 10 97 97 ether complex 6 1.67acetonitrile p-toluene- 5.3 50 3 97 96 sulfonic acid 7 1.67 acetonitrilemagnesium bromide 54.3 50 3 98 98 8 1.67 THF trifluoroacetic 6.5 40 1 9695 acid 9 1.67 acetonitrile aluminum chloride 16.7 25 10 97 97 10 1.67ethyl acetate titanium tetra- 16.7 25 10 96 96 chloride 11 1.67acetonitrile silicon tetra- 8.4 50 5 96 96 chloride

1. A method of producing a spirofluorenol compound represented by thefollowing formula (1),

by protecting a hydroxyl group bonded to a fluorenone compoundrepresented by the following formula (2),

with a protecting group which is a substituted silyl group in which thesum of carbon atoms of substituents bonded to a silicon atom is 5 to 12,then, reacting the fluorenone compound with an organometal compoundrepresented by the following formula (3),

wherein M is Li, MgCl, MgBr, MgI or CuLi, to thereby obtain ahydroxy-arylfluorenol of which the hydroxyl group is protected with saidprotecting group, and transforming the obtained hydroxy-arylfluorenolinto a spiro form and removing the protection therefrom, wherein in theabove formulas (1) to (3): X is either a single bond or a divalent groupselected from the following group A; Y is a group forming an aromatichydrocarbon cyclic group or an unsaturated heterocyclic group togetherwith two carbon atoms of a benzo ring; when X is a single bond, R¹ andR² are, respectively, hydrogen atoms or monovalent groups selected fromthe following group B, or are bonded together to form a divalent groupselected from the following group A (except, -Z- and —CR⁵R⁶—); when X isa group selected from the group A, R¹ and R² are, respectively, hydrogenatoms or monovalent groups selected from the following group B; R³ andR⁴ are, respectively, hydrogen atoms or monovalent groups selected fromthe following group B; and p and q are, independently from each other,integers of 0 to 3; group A: -Z-, —(CR⁵R⁶)_(n)—, —(CR⁵R⁶)_(m)-Z-,-Z-(CR⁵R⁶)_(l)-Z-, —(CR⁵R⁶)_(a)-Z-(CR⁵R⁶)_(b)—, —(CR⁵═CR⁶)_(k)—, andCR⁵═N— wherein -Z- is —O—, —S— or —NR⁵—, R⁵ and R⁶ are, independentlyfrom each other, hydrogen atoms, or monovalent groups selected from thefollowing group B, wherein when there are a plurality of -Z-, R⁵ or R⁶in one group, the plurality of -Z-, R⁵ or R⁶ may be different from eachother, and a, b, k and 1 are, independently from each other, integers of1 to 4, and m and n are, independently from each other, integers of 1 to6; group B: alkyl group, aralkyl group, substituted or unsubstitutedaryl group, hydroxy group, alkoxy group, aralkoxy group, amino group,monosubstituted amino group, disubstituted amino group, cyano group,nitro group, halogen atom, trufluoromethyl group, substituted orunsubstituted heterocyclic group having a bond on a carbon atom or on anitrogen atom, and substituted or unsubstituted condensed heterocyclicgroup to which aromatic hydrocarbon ring or hetero ring is condensed andhaving a bond on a carbon atom or on a nitrogen atom.
 2. A productionmethod according to claim 1, wherein when the fluorenone compoundrepresented by the above formula (2) has an amino group or amonosubstituted amino group, said hydroxyl group as well as said aminogroup or said monosubstituted amino group are protected with saidprotecting groups.
 3. A production method according to claim 1, whereinthe protection by using said substituted silyl group is conducted in thepresence of a compound represented by the following formula (4),

wherein i is an integer of 2 to 4, and j is an integer of 3 to
 6. 4. Aproduction method according to claim 1, wherein the protection isremoved from the spirofluorenol by the reaction with a quaternaryammonium fluoride or with a fluoride of an alkali metal, saidspirofluorenol being obtained by transforming the hydroxy-arylfluorenolprotected by said protecting group into a spiro form.
 5. A productionmethod according to claim 3, wherein the protection is removed from thespirofluorenol by the reaction with an alcohol or with water in thepresence of the compound represented by the above formula (4), saidspirofluorenol being obtained by transforming the hydroxy-arylfluorenolprotected by said protecting group into a spiro form.
 6. A productionmethod according to claim 1, wherein the hydroxy-arylfluorenol protectedby said protection group is transformed into a spiro form and from whichthe protection is removed in one step by being reacted with an acid inan acetonitrile solvent.
 7. A production method according to claim 6,wherein, as the acid, there is used at least the one compound selectedfrom the group consisting of boron trifluoride ether complex, magnesiumbromide, paratoluenesulfonic acid, aluminum chloride and trifluoroaceticacid.